Circulating Endometrial Cells in Women With Spontaneous Pneumothorax.

BACKGROUND: The occurrence of catamenial pneumothorax (CP) is rare, and the awareness of this diagnosis among physicians is insufficient. CP is highly correlated with pelvic endometriosis and remains the most common form of thoracic endometriosis syndrome. Circulating endometrial cells (CECs) have been previously detected in patients with pelvic endometriosis. Could CECs bring new insights into pneumothorax management? METHODS: This study aims to describe the occurrence and molecular characteristics of CECs in women with spontaneous pneumothorax (SP) (N = 20) with high suspicion of its catamenial character. CECs were enriched from peripheral blood by size-based separation (MetaCell). In addition to cytomorphology, gene expression profiling of captured cells was performed for 24 endometriosis-associated genes. RESULTS: CECs were present in all 20 patients with SP. Enriched CECs exhibited four character features: epithelial, stem cell-like, stroma-like, and glandular. However, not all of them were present in every sampling. Gene expression profiling revealed two distinct phenotypes of CECs in SP and/or CP: one of them refers to the diaphragm openings syndrome and the other to endometrial tissue pleural implantations. Comparisons of the gene expression profiles of CECs in pneumothorax (CECs-SP group) with CECs in pelvic endometriosis (CECs-non-SP group) have revealed significantly higher expression of HER2 in the CECs-SP group compared with the CECs-non-SP group. CONCLUSIONS: This proof-of-concept study demonstrates successful isolation and characterization of CECs in patients with SP. Identification of CECs in SP could alert endometriosis involvement and help early referral to gynecologic consultation for further examination and treatment.

25-hydroxyvitamin D in malignant pleural disease: a prospective cohort study.

INTRODUCTION: Growing evidence suggests a role of vitamin D in various cancers but the significance of vitamin D in malignant pleural disease remains unexplored. We sought to investigate the concentration and diagnostic role of 25-hydroxyvitamin D (25(OH)D) in malignant pleural effusions. MATERIALS AND METHODS: Prospective study of consecutive treatment-naïve patients with a new diagnosis of pleural effusion. RESULTS: Seventy-eight patients were studied, 45 of whom had malignant pleural effusions. Concentration of 25(OH)D in pleural fluid was significantly higher than serum in both malignant (15.2 ng/mL (9.7, 25.6) versus 10.2 ng/mL (6.4, 17.7), P < .001) and benign (11.4 ng/mL (8.4, 23.6) versus 7.9 (5.9, 16.1), P < .001) pleural disease. Pleural fluid 25(OH)D was almost significantly higher in exudates compared to transudates (P = .050) but it did not differ significantly between malignant and benign effusions (P = .217) and it was not diagnostic for malignant pleural disease (area under the ROC curve .58, 95% CI .45-.71). CONCLUSIONS: In subjects with unselected pleural effusions, 25(OH)D in pleural fluid was not diagnostic for malignant pleural disease. The novel finding of convincingly and consistently higher 25(OH)D in pleural fluid than serum suggests a role for vitamin D in pleural disease and merits further research.

Early effects of fluoro-edenite: correlation between IL-18 serum levels and pleural and parenchymal abnormalities.

Fluoro-edenite (FE) is a natural mineral asbestos-like fibrous species first isolated in Biancavilla, Sicily. In order to clarify potential involvement of IL-18 in the pathogenesis of FE-induced chest abnormalities, we analyzed IL-18 serum levels in FE-exposed workers (FEEW) and correlated them with pleural and parenchymal abnormalities. A total of 21 FEEWs, residing in Biancavilla for >30 years, with a working seniority of 17 ± 6.1 years were examined. High-resolution computed tomography scans revealed low grade of fibrosis in 8 (38%) FEEWs, and pleural plaques (PPs) in 13 (62%) FEEWs. The mean IL-18 level was 203.13 ± 90.43 pg/ml. Pearson correlation showed a significant association (p < 0.0001) between IL-18 and PPs and parenchymal abnormality scores. Data suggest a potential role of IL-18 in the pathogenesis of these diseases.

Hemodynamic, ventilatory and gasometric evaluation of an experimental bronchopleural fistula.

PURPOSE: To investigate the hemodynamic and ventilatory changes associated with the creation of an experimental bronchopleural fistula (BPF) treated by mechanical ventilation and thoracic drainage with or without a water seal. METHODS: Six large white pigs weighing 25 kg each which, after general anesthesia, underwent endotracheal intubation (6mm), and mechanically ventilation. Through a left thoracotomy, a resection of the lingula was performed in order to create a BPF with an output exceeding 50% of the inspired volume. The chest cavity was closed and drained into the water sealed system for initial observation of the high output BPF. RESULTS: Significant reduction in BPF output and PaCO2 was related after insertion of a water-sealed thoracic drain, p< 0.05. CONCLUSION: Insertion of a water-sealed thoracic drain resulted in reduction in bronchopleural fistula output and better CO2 clearance without any drop in cardiac output or significant changes in mean arterial pressure.

Hemodynamic, ventilatory and gasometric evaluation of an experimental bronchopleural fistula

PURPOSE: To investigate the hemodynamic and ventilatory changes associated with the creation of an experimental bronchopleural fistula (BPF) treated by mechanical ventilation and thoracic drainage with or without a water seal. METHODS : Six large white pigs weighing 25 kg each which, after general anesthesia, underwent endotracheal intubation (6mm), and mechanically ventilation. Through a left thoracotomy, a resection of the lingula was performed in order to create a BPF with an output exceeding 50% of the inspired volume. The chest cavity was closed and drained into the water sealed system for initial observation of the high output BPF. RESULTS: Significant reduction in BPF output and PaCO2 was related after insertion of a water-sealed thoracic drain, p< 0.05. CONCLUSION: Insertion of a water-sealed thoracic drain resulted in reduction in bronchopleural fistula output and better CO2 clearance without any drop in cardiac output or significant changes in mean arterial pressure. .

Idiopathic pleuroparenchymal fibroelastosis is characterized by an elevated serum level of surfactant protein-D, but Not Krebs von den Lungen-6.

PURPOSE: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported rare disease entity characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes in idiopathic interstitial pneumonias (IIPs). Because the clinical features of this rare disease are not fully elucidated, we examined the clinical characteristics of IPPFE, especially for serum interstitial biomarkers, surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6). METHODS AND RESULTS: Four consecutive cases of IPPFE who fulfilled the diagnostic criteria were studied. All cases were more than 60 years of age, and were classified as underweight by body mass index. A severe restrictive ventilatory defect was found in all cases on admission. High-resolution computed tomography showed intense pleural thickening associated with fibrosis predominant in upper lobes. Histopathological findings were also confirmed in three out of four cases. Interestingly, the serum level of SP-D was markedly elevated in all cases, while KL-6 was within normal range in three out of four cases. As compared with major IIPs such as idiopathic pulmonary fibrosis and fibrotic nonspecific interstitial pneumonia, IPPFE significantly showed higher frequency of cases with a unique pattern of serum biomarkers, which is characterized by an elevated level of SP-D with a normal range of KL-6. CONCLUSIONS: In IPPFE, SP-D might tend to be elevated, while KL-6 was within a normal range. Further study is required to determine the pathogenesis and clinical significance of the elevated SP-D in IPPFE.

Ability of procalcitonin to discriminate infection from non-infective inflammation using two pleural disease settings.

UNLABELLED: Procalcitonin has been shown to be useful in separating infection from non-infective disorders. However, infection is often paralleled by tissue inflammation. Most studies supporting the use of procalcitonin were confounded by more significant inflammation in the infection group. Few studies have examined the usefulness of procalcitonin when adjusted for inflammation.Pleural inflammation underlies the development of most exudative effusions including pleural infection and malignancy. Pleurodesis, often used to treat effusions, involves provocation of intense aseptic pleural inflammation. We conducted a two-part proof-of-concept study to test the specificity of procalcitonin in differentiating infection using cohorts of patients with pleural effusions of infective and non-infective etiologies, as well as subjects undergoing pleurodesis. METHODS: We measured the blood procalcitonin level (i) in 248 patients with pleural infection or with non-infective pleural inflammation, matched for severity of systemic inflammation by C-reactive protein (CRP), age and gender; and (ii) in patients before and 24-48 hours after induction of non-infective pleural inflammation (from talc pleurodesis). RESULTS: 1) Procalcitonin was significantly higher in patients with pleural infection compared with controls with non-infective effusions (n = 32 each group) that were case-matched for systemic inflammation as measured by CRP [median (25-75%IQR): 0.58 (0.35-1.50) vs 0.34 (0.31-0.42) µg/L respectively, p = 0.003]. 2) Talc pleurodesis provoked intense systemic inflammation, and raised serum CRP by 360% over baseline. However procalcitonin remained relatively unaffected (21% rise). 3) Procalcitonin and CRP levels did not correlate. In 214 patients with pleural infection, procalcitonin levels did not predict the survival or need for surgical intervention. CONCLUSION: Using a pleural model, this proof-of-principle study confirmed that procalcitonin is a biomarker specific for infection and is not affected by non-infective inflammation. Procalcitonin is superior to CRP in distinguishing infection from non-infective pleural diseases, even when controlled for the level of systemic inflammation.

Levels of YKL-40 in pleural effusions and blood from patients with pulmonary or pleural disease.

BACKGROUND: YKL-40 (a chitinase-like protein) is an inflammatory biomarker that is associated with lung injury pathogenesis. We aimed to identify the diagnostic values of YKL-40 in pleural effusions and to evaluate circulating YKL-40 levels during multiple etiological pulmonary/pleural diseases and the role of YKL-40 as a monitoring marker of inflammatory pulmonary disease. METHODS: Pleural YKL-40 (n=197), YKL-39 (the most homologous chitinase-like protein to human YKL-40), and conventional pleural marker levels were measured in patients with pulmonary/pleural disease. Additionally, serum YKL-40 and YKL-39 levels were analyzed in both patients and controls (n=432) and serially monitored in patients with asthma (n=27) or pneumonia (n=22). RESULTS: Pleural YKL-40 levels were higher than those in the serum and highest in tuberculous pleural effusions (TPEs; 1181 ng/mL), followed by parapneumonic, malignant, and cardiogenic effusions (560 ng/mL). The diagnostic accuracy of pleural YKL-40 (0.78) for discriminating between tuberculous and malignant effusion was comparable to or greater than those of YKL-39, total protein, C-reactive protein and CYFRA 21-1, and lower than those of adenosine deaminase (p<0.05) and carcinoembriogenic antigen (p=0.05). Serum YKL-40 levels were higher in the pneumonia group than in the cancer, asthma, or control groups. Following treatment, serum YKL-40 levels were more greatly reduced in pneumonia patients than in asthma patients. Serum YKL-39 levels did not differ between patients and controls. CONCLUSIONS: Pleural YKL-40 levels are elevated in TPEs and have fairly good diagnostic efficacy for detecting TPEs. However, adenosine deaminase is more efficient for detecting TPEs than pleural YKL-40. Serum YKL-40 levels are highest during pneumonia compared to common pulmonary/pleural diseases and are more useful for monitoring pneumonia than asthma.

Osteopontin, asbestos exposure and pleural plaques: a cross-sectional study.

BACKGROUND: Osteopontin (OPN) is a plasma protein/cytokine produced in excess in several malignancies. In a recent study OPN was reported as being related to the duration of asbestos exposure and presence of benign asbestos-related diseases; however, it was unclear whether this protein was an indicator of exposure or effect. METHODS: In 193 workers, 50 with pleural plaques (PP), in whom different indicators of past asbestos exposure were estimated, OPN plasma levels were assessed using commercial quantitative sandwich enzyme immunoassays according to the manufacturer's instructions. RESULTS: Osteopontin increased with increasing age and several aspects of asbestos exposure, without differences related to the presence of pleural plaques. At multivariable regression analysis, the explanatory variables with a significant independent influence on OPN were length of exposure (positive correlation) and time elapsed since last exposure (positive correlation). CONCLUSIONS: Since asbestos in lung tissue tends to wane over time, OPN should decrease (rather than increase) with time since last exposure. Therefore, OPN cannot be a reliable biomarker of exposure nor effect (presence of pleural plaques).

Evaluation of ovarian cancer biomarkers in subjects with benign asbestos-related pleural diseases.

BACKGROUND: Mesothelioma and ovarian cancer have been reported to have a similar pathogenesis, and for this reason it was hypothesized that there may be biomarkers in common and possibly associated with benign pleural diseases caused by asbestos exposure. METHODS: Serum biomarkers including insulin-like growth factor-II (IGF-II), leptin, prolactin and vascular endothelial growth factor (VEGF) were measured in an observational study of subjects with benign asbestos-related pleural diseases (BARPD) (n=24) and healthy subjects with an asbestos exposure history (n=12). RESULTS: Mean serum IGF-II and VEGF concentration in healthy subjects with a history of asbestos exposure were higher than those with BARPD. Mean serum concentrations of leptin and prolactin showed opposite trends when compared to IGF-II and VEGF concentrations among these groups. CONCLUSIONS: The results suggest that IGF-II and VEGF concentrations are lower in BARPD, similar to studies of ovarian cancer. This finding warrants further investigation with malignant asbestos-related diseases.

Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease.

PURPOSE: The aim of this study was to compare the results of semiquantitative analysis by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) with plasma osteopontin levels in the same asbestos-related pleural disease population. MATERIALS AND METHODS: A total of 17 patients with asbestos-related pleural disease were prospectively recruited. They underwent PET/CT, and plasma osteopontin levels were measured. The maximum standardized uptake value (SUVmax) was determined from the most active pleural lesion in each patient. RESULTS: Malignant pleural mesothelioma (MPM) was histologically proven in 6 patients, and 11 patients had proven benign asbestos-related pleural diseases (7 pleural plaques, 4 asbestos pleurisy). Significant differences in SUVmax were found between patients with MPM and those with asbestos pleurisy (P = 0.031) and between patients with MPM and those with pleural plaques (P = 0.012). A significant difference was found in the plasma osteopontin levels between patients with asbestos pleurisy and patients with pleural plaques (Bonferroni correction, P = 0.024). The SUVmax in patients with benign asbestos-related diseases was statistically positively correlated with plasma osteopontin in the same group (Spearman's r = 0.75, P < 0.05). CONCLUSION: PET/CT might be more helpful than plasma osteopontin for distinguishing benign asbestos-related pleural diseases from MPM, and the SUVmax in benign asbestos-related pleural diseases may reflect changes in pleural inflammation.

Preoperative hypoalbuminemia is a risk factor for late bronchopleural fistula after pneumonectomy.

BACKGROUND: Pneumonectomy is still a high-risk surgical procedure. Postpneumonectomy bronchopleural fistula is an especially severe complication with a high mortality rate. Although several reports have discussed risk factors for early bronchopleural fistula after pneumonectomy, only a few have reported them for late bronchopleural fistula. We reviewed cases of late bronchopleural fistula after pneumonectomy and investigated its risk factors. METHODS: Sixty-four patients with nonsmall cell lung cancer underwent pneumonectomy at our institution from June 1999 to December 2004. Among them, 5 who developed bronchopleural fistula were investigated. RESULTS: All of the 5 patients were male; 3 had undergone right pneumonectomy and 2 left pneumonectomy. The period between surgery and the appearance of bronchopleural fistula ranged from 36 to 164 days. We found that the preoperative serum albumin level was significantly lower in the patients with late bronchopleural fistula. Induction therapy, surgical side, age, anemia, arterial blood oxygen, and respiratory function did not affect the occurrence of bronchopleural fistula after pneumonectomy. CONCLUSIONS: A preoperative low-serum albumin level, indicative of poor nutritional status, is a risk factor for late bronchopleural fistula after pneumonectomy for nonsmall cell lung cancer.

Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax.

The thorax is the most frequent extrapelvic location of endometriosis. Thoracic endometriosis is probably responsible for the high rate of recurrent pneumothoraces in females. The goal of the present prospective study was to assess the value of cancer antigen (CA)125 measurement in the detection of endometriosis in order to further enable early and adequate treatment of catamenial pneumothorax. Between January 2004 and March 2006, 31 females (mean age 32 yrs) underwent pneumothorax surgery. The control group comprised 17 males (mean age 27 yrs), who underwent videothoracoscopic pleural abrasion. Serum CA125 was measured around a menstrual period in females and before surgery in males. Videothoracoscopically diagnosed endometriosis occurred in 29% of females. The CA125 concentration was significantly higher in females with endometriosis compared to disease-free females (76.1 versus 16 U x mL(-1)). The mean value in males was similar to that observed in disease-free females. The frequency of thoracic endometriosis-related pneumothorax corresponds to, on average, a third of females presenting with recurrent pneumothorax. Early detection can be achieved with serum cancer antigen 125 measurement and may be helpful in indicating videothoracoscopic surgery.

Preoperative serum fibrinogen level predicts postoperative pulmonary complications after lung cancer resection.

BACKGROUND: Patients undergoing pulmonary resection are thought to be at high risk for the development of postoperative pulmonary complications (PPCs), and these complications may lead to serious morbidity. The purpose of this study was to identify the factors associated with postoperative pulmonary complications in patients undergoing lung cancer resection and to determine the effect of PPCs on survival. METHODS: The study involved a retrospective review of 635 patients who had undergone curative resection for lung cancer. The patient group included 504 males (79.4%), and the overall mean age was 61.3 years. Patients were classified as those who had experienced PPCs (PPCs group, n = 105, 16.5%) or those who had not (no-PPCs group, n = 530, 83.5%). RESULTS: The surgical procedures performed were 101 pneumonectomies (15.9%), 505 lobectomies (79.5%), and 29 lesser resections (4.6%). Cancer types comprised 330 squamous cell carcinomas (52.0%), 255 adenocarcinomas (40.2%) and 50 others (7.8%). Univariate analysis showed that the following factors were predictors for PPCs: male sex, erythrocyte sedimentation rate, preoperative serum fibrinogen level, pulmonary function, chronic obstructive pulmonary disease, smoking, double primary cancer, and surgical duration. Multivariate logistic regression showed that preoperative serum fibrinogen level (p < 0.001), surgical duration (p < 0.0001) and being male (p = 0.02) were significant predictors of PPCs. Overall survival 3 years after surgery was 68.2% in no-PPCs group and 38.8% in PPCs group (p < 0.0001). Regardless of tumor staging, overall survival differed significantly between PPCs and no-PPCs groups, whereas disease-free survival did not. CONCLUSIONS: Higher preoperative serum fibrinogen levels, longer surgical duration, and being male were the predictive factors for PPCs in surgical candidates. The development of PPCs was linked to a shortened overall survival.

Pleural amyloidosis as the first sign of IgD multiple myeloma.

We describe a case of IgD myeloma with amyloid and plasmocytic pleural localisations. At the onset of the disease it mimicked rheumatoid arthritis, which can be the first presentation of both AL amyloidosis and multiple myeloma. Pleural effusion can happen first in IgD myeloma, but our observation is of interest in that it confirms the very rare possibility of pleural amyloid and plasmocytic localisations devoid of pleural effusion.

Mesothelin-family proteins and diagnosis of mesothelioma.

BACKGROUND: Mesothelioma is a highly aggressive tumour for which there are no reliable serum tumour markers. Identification of such a marker would be useful in diagnosis of mesothelioma and for monitoring responses to treatment and screening at-risk individuals. METHODS: We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases. FINDINGS: 37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma. INTERPRETATION: Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma.

SV40, JC and BK expression in tissue, urine and blood samples from patients with malignant and nonmalignant pleural disease.

BACKGROUND: Polyomaviruses are expressed in both human tumors and immunodepressed patients. Malignant and nonmalignant pleural effusions create an environment that could favor the expression of opportunistic viral infections. We studied if SV40, JC, and BK viral DNA can be amplified from biopsies obtained from different pleural diseases. MATERIALS AND METHODS: DNA was extracted from mesotheliomas (MM), nonspecific inflammatory and tubercular pleural biopsies, blood and urinary sediments from patients with MM, and pleural effusion cytological specimens. SV40, JC and BK viral early regions were amplified by PCR and analyzed by Southern Blot hybridization with specific probes. RESULTS: SV40 was positive in 9/23 MM, 5/18 tubercular and 1/7 nonspecific inflammatory biopsies, and 5/12 pleural effusion cytological specimens. JC was positive in 2/23 MM and in 7/15 urinary sediments. All blood samples were negative and BK was also negative in all samples. CONCLUSIONS: Tissue specific factors, characteristic of MM and TB, may contribute to expression of SV40 in these diseases.

Increased serum concentrations of growth factor receptors and Neu in workers previously exposed to asbestos.

OBJECTIVES: Epidermal growth factor receptor (EGFR) and oncogene Neu belong to a family of growth factor receptors which may play a part in carcinogenesis. Although increased serum concentrations of Neu and EGFR have been shown in several patients with asbestosis who later developed cancer, serum concentrations have not been studied in workers exposed in the past to asbestos but without asbestos related diseases. METHODS: Serum concentrations of secreted growth factor receptors were studied in 300 workers exposed in the past to asbestos and the results were compared with those of 70 controls. RESULTS: In the controls 4.3% (3/70) had EGFR values > 912 units/ml, compared with 39% (117/299) of the exposed group (p < 0.001). The difference in high values was even more pronounced for Neu with 4.3% of controls having Neu values > 2580 fmol/ml compared with 72% (216/299) of the exposed workers (p < 0.001). Pleural plaques predicted lower serum concentrations of EGFR but not lower Neu concentrations, and this finding remained significant after adjustment for age, exposure time, smoking, and time from initial exposure. CONCLUSIONS: Enhanced secretion of EGFR and Neu was found in a large cohort of retired asbestos workers with a wide range of exposure and latency periods. They did not have asbestosis or cancer and their EGFR values were higher in those without plaques. Further studies are needed to confirm our results, to determine the source of the secreted growth factor receptors, and to study their possible value as risk factors in the development of cancer.